Cholesteryl Ester Transferase Protein (CETP) is a 74-kDa glycoprotein and has hydrophobic characteristic.1 This protein is primarily synthesized in liver and secreted to the plasma. In addition, CETP is also expressed in lower concentration in lymph, adipose tissue, heart, renal, and small intestine.2 CETP plays a role in the Reverse Cholesterol Transport (RCT) process, where this protein mediates the exchange of cholesteryl ester in high density lipoprotein (HDL) particle for triglycerides in low density lipoprotein (LDL) and very low density lipoprotein (VLDL) particles.1,3-5 Many prior studies had showed that CETP accelerates the cholesteryl ester accumulation process in LDL particle that leads to the inhibition of the elimination process of cholesterol from blood circulation.4 It is reported in epidemiological studies that subjects with genetically CETP deficiency have higher amount of HDL cholesterol and lower amount of LDL cholesterol. Therefore, CETP becomes a potential therapy target in drug discovery for dyslipidemia and atherosclerosis treatment.
Nowadays, studies which emphasize at CETP are being conducted as the efforts of studying the CETP activities and its effects on the changes of HDL cholesterol and triglyceride levels in human blood plasma.5,6 A high amount of HDL cholesterol as the result of the decrease in CETP expression is very important, whereby it has been reported that there is a negative correlation between HDL cholesterol level and the atherosclerosis risk factors.7 The atheroprotective property of HDL is in its role in the RCT process where the excessive cholesterol in peripheral cell are distributed to the liver to be excreted.6 There are some CETP inhibitors that have been produced and learned, such as cholesteryl ester transferase protein inhibitory peptides and CETP antisense oligodeoxynucleotides (ODNs).8,9 However, those two inhibitors are still being studied. Besides, there was a drug as CETP inhibitor which had been developed up to clinical trial, namely torcetrapib. This product, however, did not give a positive result in the clinical trials, considering a high number of mortality in patients consuming that drug.10 After being studied further, torcetrapib caused an increase in patients' blood pressure that led to death.
It is taught, in this present invention, the extraction process and the use of one of herbal plants, Phaleria macrocarpa. Phaleria macrocarpa, locally known as mahkota dewa, is an Indonesian native plant, usually found in yards as decorative plant or in garden as shade plant. Surprisingly, this plant, by utilizing its stems, fruit flesh, or leaves, is able to serve as CETP inhibitor. Prior to this invention, there has not been any study which explains the use or benefit of Phaleria macrocarpa extract as CETP inhibitor as claimed in this invention.